We have isolated and characterized an antigen-specific inducer activity and an antigen-specific suppressor activity each present in the same human leukocyte dialyeate fraction (greater than 3500 less than 12,000) prepared from immune donors using the leukocyte migration inhibition (LMI) assay. Inducer activity: binds to specific antigen, to anti-VH, to anti-Ia and is a product of T(H) not Ts cells that is selectively absorbed by T(S) cells and by macrophages. The inducer converts non-immune cells to specific immune reactivity. It appears to be a dialyzable fragment of VH region of a T-cell receptor. Suppressor activity: binds to specific IgG, to anti VK, to anti-Ia and is a product of T(S) and not T(H) cells. The suppressor binds to T(H) cells and abrogates the response of immune cells to antigen and blocks the effect of inducer activity on non-immune cells in vitro and suppreses the footpad reaction of immunized mice to specific antigen in vivo. It appears to be a dialysable fragment of an anti-idiotypic T-cell receptor. Both inducer activity and suppressor activity have no MHC or species restriction and appear to function as opposing activities of an immunoregulatory network. We have also shown that dialysates from 0 cell-enriched murine LNC possess inducer activity for human cell populations in the LMI assay and in the transfer of DTH between BALB/c mice to microbial antigens in vivo. Specific Aims: 1. To evaluate the in vivo effects of dialysable human inducer and suppressor activity on the induction and suppression of DTH footpad responses in BALB/c mice to microbial antigens. 2. To evaluate the in vivo effects of dialysable murine inducer and suppressor activity prepared from 0 cell enriched lymph node lymphocytes in BALB/c mice and to determine the lymphocyte subpopulation (e.g. Ly1+2-3-, Ly1-2+3+) responsible for the production as well as that serving as the target cell for each activity. 3. To test murine inducer and suppressor activities for the presence of V-region, Ia region and MNC-region determinants by absorption studies with defined antisera. 4. To evaluate the in vivo effects of dialysable murine inducer and suppressor activity prepared from appropriate lymphocyte subpopulations obtained from high responder and low responder donor mice upon the DTH footpad response of high and low responder recipient mice to polymeric antigens (eg. TGAL, GAL, GAT), 5. To continue current screening of a human T-cell hybridoma for the production of specific inducer/suppressor activity.